E-EROS Editorial Board

Handbook of Reagents for Organic Synthesis Sulfur-Containing Reagents OTHER TITLES IN THIS COLLECTION

Reagents for Radical and Radical Ion Chemistry Edited by David Crich ISBN 978 0 470 06536 5 Catalyst Components for Coupling Reactions Edited by Gary A. Molander ISBN 978 0 470 51811 3 Fluorine-Containing Reagents Edited by Leo A. Paquette ISBN 978 0 470 02177 4 Reagents for Direct Functionalization of C–H Bonds Edited by Philip L. Fuchs ISBN 0 470 01022 3 Reagents for Glycoside, Nucleotide, and Peptide Synthesis Edited by David Crich ISBN 0 470 02304 X Reagents for High-Throughput Solid-Phase and Solution-Phase Organic Synthesis Edited by Peter Wipf ISBN 0 470 86298 X Chiral Reagents for Asymmetric Synthesis Edited by Leo A. Paquette ISBN 0 470 85625 4 Activating Agents and Protecting Groups Edited by Anthony J. Pearson and William R. Roush ISBN 0 471 97927 9 Acidic and Basic Reagents Edited by Hans J. Reich and James H. Rigby ISBN 0 471 97925 2 Oxidizing and Reducing Agents Edited by Steven D. Burke and Rick L. Danheiser ISBN 0 471 97926 0 Reagents, Auxiliaries, and Catalysts for C–C Bond Formation Edited by Robert M. Coates and Scott E. Denmark ISBN 0 471 97924 4

e-EROS For access to information on all the reagents covered in the Handbooks of Reagents for Organic Synthesis, and many more, subscribe to e-EROS on the Wiley Interscience website. A database is available with over 200 new entries and updates every year. It is fully searchable by structure, substructure and reaction type and allows sophisticated full text searches. http://www.mrw.interscience.wiley.com/eros/ Handbook of Reagents for Organic Synthesis Sulfur-Containing Reagents

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Library of Congress Cataloging-in-Publication Data

Handbook of reagents for organic synthesis. p.cm Includes bibliographical references. Contents: [1] Reagents, auxiliaries and catalysts for C–C bond formation / edited by Robert M. Coates and Scott E. Denmark [2] Oxidizing and reducing agents / edited by Steven D. Burke and Riek L. Danheiser [3] Acidic and basic reagents / edited by Hans J. Reich and James H. Rigby [4] Activating agents and protecting groups / edited by Anthony J. Pearson and William R. Roush [5] Chiral reagents for asymmetric synthesis / edited by Leo A. Paquette [6] Reagents for high-throughput solid-phase and solution-phase organic synthesis / edited by Peter Wipf [7] Reagents for glycoside, nucleotide and peptide synthesis / edited by David Crich [8] Reagents for direct functionalization of C–H bonds/edited by Philip L. Fuchs [9] Fluorine- Containing Reagents/edited by Leo A. Paquette [10] Catalyst Components for Coupling Reactions / edited by Gary A. Molander [11] Reagents for Radical and Radical Ion Chemistry/edited by David Crich [12] Sulfur-Containing Reagents / edited by Leo A. Paquette

ISBN 0-471-97924-4 (v. 1) ISBN 0-471-97926-0 (v. 2) ISBN 0-471-97925-2 (v. 3) ISBN 0-471-97927-9 (v. 4) ISBN 0-470-85625-4 (v. 5) ISBN 0-470-86298-X (v. 6) ISBN 0-470-02304-X (v. 7) ISBN 0-470-01022-3 (v. 8) ISBN 978-0-470-02177-4 (v. 9) ISBN 978-0-470-51811-3 (v.10) ISBN 978-0-470-06536-5 (v. 11) ISBN 978-0-470-74872-5 (v.12)

1. Chemical tests and reagents. 2. Organic compounds-Synthesis. QD77.H37 1999 98-53088 547’.2 dc 21 CIP

A catalogue record for this book is available from the British Library.

ISBN 13: 978-0-470-74872-5

Set in 9½/11½ pt Times Roman by Thomson Press (India) Ltd., New Delhi. Printed in Great Britain by Antony Rowe, Chippenham, Wiltshire. This volume is dedicated to Dr. Gerald Berkelhammer who introduced me to the ﬁeld of organosulfur chemistry during summer employment (1957) as a ﬂedgling graduate student while working at the American Cyanamid Company in Stamford, Connecticut. e-EROS Editorial Board

Editor-in-Chief David Crich Institut de Chimie des Substances Naturelles (ICSN), Gif-sur-Yvette, France

Executive Editors André B. Charette Université de Montréal, Montréal, QC, Canada Philip L. Fuchs Purdue University, West Lafayette, IN, USA Gary A. Molander University of Pennsylvania, Philadelphia, PA, USA

Founding Editor Leo A. Paquette The Ohio State University, Columbus, OH, USA

Contents

Preface xiii (4R,5R)-2-Bromo-1,3-bis-(4-methylphenyl sulfonyl)-4,5-diphenyl-1,3,2-diazaborolidine and Introduction xv (4S,5S)-2-Bromo-1,3-bis-(4-methylphenyl sulfonyl)-4,5-diphenyl-1,3,2-diazaborolidine 91 Short Note on InChIs and InChIKeys xvi Bromodifluorophenylsulfanylmethane 98 Organic Syntheses Procedures Featuring the Synthesis Bromomethanesulfonyl Phenyl Tetrazole (Chloro) 100 of Organosulfur Compounds and Preparative 2-(2-Butenylthio)benzothiazole 102 Applications thereof, Volumes 65–85 1 tert-Butyl N-Lithio-N-(p-toluenesulfonyloxy)carbamate 103 2-[N-(tert-Butyloxycarbonyl)aminophenyl]ethanethiol 104 Allyl Triflone 15 tert-Butylsulfonyl Chloride 107 Aminoiminomethanesulfonic Acid 16 tert-Butyltetrazolylthiol 109 p-Anisolesulfonyl Chloride 18 10-Camphorsulfonyl Chloride 111 Anthracenesulfonamide 19 Carbomethoxysulfenyl Chloride 118 1-Benzenesulfinyl Piperidine 21 Carbon Disulfide 124 Benzenesulfonic Acid, 2-Nitro-,(1-Methylethylidene) Cerium(IV) Ammonium Sulfate 128 hydrazide 23 Cesium Fluoroxysulfate 130 Benzenesulfonic Anhydride 25 N-Chloro-N-cyclohexylbenzenesulfonamide 131 Benzenesulfonyl Bromide 26 Chloromethyl p-Tolyl Sulfide 132 Benzimidazolium Triflate 27 Chloromethyl p-Tolyl Sulfone 134 (1R,5R)-2H-1,5-Benzodithiepin-3(4H)-one 1,5-Dioxide 29 4-Chlorophenyl Chlorothionoformate 136 3H-1,2-Benzodithiol-3-one 1,1-Dioxide 31 4-(4-Chlorophenyl)-3-hydroxy-2(3H)thiazolethione 137 Benzothianthrene Oxide 34 N-Chlorosuccinimide–Dimethyl Sulfide 140 Benzothiazole-2-sulfonyl Chloride 36 Chloro(thexyl)borane–Dimethyl Sulfide 144 4-Benzyloxazolidine-2-thione 37 Copper(II) Sulfate 145 3-(2-Benzyloxyacetyl)thiazolidine-2-thione 40 Copper, (2-Thiophenecarboxylato-κO2,κS1) 152 Benzyltriethylammonium Tetrathiomolybdate 42 Copper(II) Toluenesulfonate 157 N-Benzyl Triflamide 46 Copper(I) Trifluoromethanesulfonate 158 4,4-Bis(2-amino-6-methylpyrimidyl) Disulfide 48 Copper(II) Trifluoromethanesulfonate 181 Bis(2,2-bipyridyl)silver(II) Peroxydisulfate 49 Dibromoborane–Dimethyl Sulfide 189 N,N-Bis(tert-butoxycarbonyl)-N- Dibutyl(trifluoromethanesulfoxy)stannane 197 trifluoromethanesulfonylguanidine 50 Dicarbonyl(cyclopentadienyl)[(dimethylsulfonium) [N,N-[1,2-Bis(3,5-dimethylphenyl)-1,2-ethanediyl]bis methyl]iron Tetrafluoroborate 198 (1,1,1-trifluoromethanesulfonamidato)]methylaluminum 51 Dichloroborane–Dimethyl Sulfide 200 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2-2-Difluorovinyl p-Toluenesulfonate 205 2,4-Disulfide 52 2,5-Dihydro-2,2-dimethyl-5,5-bis(propylthio)- 2,3-Bis[(4-methylphenyl)thio]-1,3,2,4-dithiadiphosphetane 1,3,4-oxadiazole 206 2,4-Disulfide 68 2,3-Dihydro-2-phenylimidazo[2,1-b]benzothiazole 207 2,4-Bis(methylthio)-1,3,2,4-dithiadiphosphetane Diisopropyl Methylsulfanyldifluoromethylphosphonate 209 2,4-Disulfide 69 4-(Dimethylamino)pyridinium Chlorosulfite N-[Bis(methylthio)methylene]-p-toluenesulfonamide 71 Chloride 211 Bis[N-(p-toluenesulfonyl)]selenodiimide 80 Dimethyl Bis(methylthio)methylphosphonate 212 1-[Bis(trifluoromethanesulfonyl)methyl]-2,3,4,5,6- 6,6-Dimethyl-1,4-diseleno-3,7-tetrasulfide 213 pentafluorobenzene 81 N,N-Dimethyldithiocarbamoylacetonitrile 214 Bis(4-trimethylsilylphenyl) Disulfide and N-(1,1-Dimethylethyl)benzenesulfenamide 215 Bis(4-trimethylsilylphenyl) Diselenide 85 N,N-Dimethyl-O-(methylsulfonyl)hydroxylamine 217 Boron Trifluoride–Dimethyl Sulfide 86 Dimethyl(methylthio)sulfonium Tetrafluoroborate 219 4-Bromobenzenesulfonyl Azide 89 Dimethyl(methylthio)sulfonium Trifluoromethane- 4-Bromobenzenesulfonyl Chloride 90 sulfonate 225 x CONTENTS cis-3-[N-(3,5-Dimethylphenyl)benzenesulfonamido] Mesitylsulfonyl-1H-1,2,4-triazole 345 borneol 230 (R,R)-1,2-(Methanesulfonamido)-cyclohexane 346 Dimethylsuccinimidosulfonium Tetrafluoroborate 231 Methanesulfonic Anhydride 349 Dimethyl Sulfoxide–Iodine 233 Methanesulfonyl Chloride–Dimethylaminopyridine 350 Dimethyl Sulfoxide–Methanesulfonic Anhydride 234 Methoxycarbonylmethanesulfonyl Chloride 351 Dimethyl Sulfoxide–Phosphorus Pentoxide 234 Methoxycarbonylsulfamoyl Chloride 351 Dimethyl Sulfoxide–Silver Tetrafluoroborate 235 4-Methoxycarbonylthiolan-3-one 352 Dimethyl Sulfoxide–Sulfur Trioxide/Pyridine 237 2-(2-Methoxyethoxy)-ethyl 2-(Chlorosulfonyl)-benzoate 354 S,S-Dimethyl-N-(p-toluenesulfonyl)sulfilimine 238 Methoxyphenyl Benzenethiosulfinate 357 S,S-Dimethyl-N-(p-toluenesulfonyl)sulfoximine 239 1-(4-Methoxyphenyl)-2-(4-methylbenzylthio)ethylamine 358 2,4-Dinitrobenzenesulfonyl Chloride 240 7-Methoxy-3-(phenylsulfonyl)-1(3H)-isobenzofuranone 361 3,5-Dinitrobenzenesulfonyl Chloride 242 Methoxy(phenylthio)methane 362 2,4-Dinitrobenzenesulfonylhydrazide 243 Methoxy(phenylthio)trimethylsilylmethane 364 2-(1,3-Dioxan-2-yl)ethylsulfonyl Chloride 244 2-Methylallyl Phenyl Sulfone 366 1,1-Dioxobenzo[b]-thiophene-2-yl Methyloxycarbonyl 2-Methylbenzothiazole 369 Chloride 246 Methylbis(methylthio)sulfonium Hexachloroantimonate 371 Diphenylbis(1,1,1,3,3,3-hexafluoro-2-phenyl-2- Methyl α-Chloro-α-phenylthioacetate 373 propoxy)sulfurane 246 Methyl Diethylamidosulfite 374 (R,R)-1,2-Diphenyl-1,2-diaminoethane Methyl Methanethiosulfonate 374 N,N-Bis[3,5-bis(trifluoromethyl)benzenesulfonamide] 248 4-Methyl-N-phenylbenzene Sulfonimidoyl Chloride 377 N-(Diphenylmethylene)benzenesulfonamide and 1-Methyl-2(1H)-pyridinethione 380 N-(Diphenylmethylene)-4-methylbenzenesulfonamide 250 Methylsulfenyl Trifluoromethanesulfonate 380 Diphenyl Sulfoxide 253 (+)-(S)-N-Methylsulfonylphenylalanyl Chloride 381 2,2-Dipyridyl Disulfide-N,N-dioxide 258 2-Methylsulfonyl-3-phenyl-1-prop-2-enyl 1,2,4-Dithiazolidine-3,5-dione 262 Chloroformate 382 1,3-Dithienium Tetrafluoroborate 266 Methyl Thioglycolate 384 trans-1,3-Dithiolane 1,3-Dioxide 267 Methylthiomaleic Anhydride 385 1,4-Dithiothreitol 268 1-(Methylthiomethyl)benzotriazole 386 tert-Dodecanethiol 269 Methylthiomethyl p-Tolyl Sulfone 387 p-Dodecylbenzenesulfonyl Azide 272 (E)-3-Methylthio-2-propenyl p-Tolyl Sulfone 390 Ethyl (Dimethylsulfuranylidene)acetate 275 2-(Methylthio)tetrahydrofuran 391 S-Ethyl Ethanethiosulfinate 279 5-Methylthio-1H-tetrazole 391 4-Ethylhexahydro-4-methyl-(4S,9aS)- Methyl N-(p-Toluenesulfonyl)carbamate 392 pyrrolo[1,2-d][1,4]thiazepin-5(4H)-one 282 α-Methyltoluene-2,α-sultam 395 5-Ethylthio-1H-tetrazole 283 Methyl p-Toluenethiosulfonate 397 2-Fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole N-Methyltrifluoromethanesulfonamide 398 1,1-Dioxide 287 Methyltrifluoromethanesulfonate 399 N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide 288 (−)-2-exo-Morpholinoisobornane-10-thiol 408 Fluorosulfuric Acid 291 o-Nitrobenzenesulfonyl Azide 411 Fluorosulfuric Acid–Antimony(V) Fluoride 294 o-Nitrobenzenesulfonyl Chloride 412 Glyoxylyl Chloride p-Toluenesulfonylhydrazone 299 o-Nitrobenzenesulfonylhydrazide 415 2-Hydroxyethyl Phenyl Sulfone 305 p-Nitrobenzenesulfonyl-4-nitroimidazole 417 [Hydroxy(tosyloxy)iodo]benzene 307 p-Nitrobenzenesulfonyloxyurethane 418 Isopropyldiphenylsulfonium Tetrafluoroborate 317 5-Nitro-3H-1,2-benzoxathiole S,S-Dioxide 419 (S)-4-Isopropylthiazolidine-2-thione 318 Nitrosylsulfuric Acid 420 (1R,2S)-1-Lithio-1-phenylsulfonyl-2- 1,1,1,2,2,3,3,4,4-Nonafluoro-6-(methanesulfinyl)hexane 422 [(tert-butyldiphenyl)silyl]oxymethyloxirane 321 Oxodimethoxyphosphoranesulfenyl Chloride 425 2-Lithio-N-phenylsulfonylindole 323 Pentafluorosulfanyl Chloride 427 Lithium Butyl(phenylthio)cuprate 325 1H,1H,2H,2H-Perfluorodecanethiol 428 Lithium Cyclopropyl(phenylthio)cuprate 326 Peroxydisulfuryl Difluoride 430 Lithium (3,3-Diethoxy-1-propen-2-yl)(phenylthio)cuprate 327 Phenyl Chlorothionocarbonate 432 Lithium 2-Lithiobenzenethiolate 329 1-Phenyl-2-(phenylsulfanyl)ethyl Acetate 434 Lithium 1-Methyl-2-(2-methyl-1-(E)-propenyl)- 4-Phenylsulfonyl-2-butanone Ethylene Acetal 436 cyclopropyl(phenylthio)cuprate 330 N-(Phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine 437 Lithium Phenylthio(trimethylstannyl)cuprate 333 (2-Phenylsulfonyl)ethoxy Dichlorophosphine 439 Lithium Phenylthio(2-vinylcyclopropyl)cuprate 334 α-Phenylsulfonylethyllithium 440 (−)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate 337 (2-Phenylsulfonylethyl)trimethylsilane 444 6-Mercapto-4-dibenzofuranol 340 Phenylsulfonylfluoromethylphosphonate 445 1-(Mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT) 342 (1S,6S)-2-(Phenylsulfonyl)-7-oxabicyclo[4.1.0]hept-2-ene 446 CONTENTS xi

(E,E)-N-Phenylsulfonyl-4-phenyl-1-aza-1,3-butadiene 449 (R)-(+)-3-(p-Tolylsulfinyl)propionic Acid 557 3-(Phenylsulfonyl)propanal Ethylene Acetal 451 Tosyl Azide, Polymer-supported 558 1-Phenylsulfonyl-1H-tetrazole 452 β-Tosylethylamine 559 (E)-1-Phenylsulfonyl-2-trimethylsilylethylene 453 β-Tosylethylazide 560 1-Phenyl-2-tetrazoline-5-thione 454 6-Tosyl-3-oxa-6-azabicyclo[3.1.0]hexane 561 2-Phenylthioethanol 456 Tri(tert-butoxy)silanethiol 563 (Phenylthio)nitromethane 457 Tricarbonyl[(2,3,4,5,6,7-η)-thiepin-1,1- N-Phenylthiophthalimide 459 dioxide]chromium(0) 566 1-Phenylthiovinyl Triphenylphosphonium Iodide 460 2,2,2-Trichloroethoxysulfonamide 568 Se-Phenyl p-Tolueneselenosulfonate 461 2,2,2-Trichloroethyl-N-tosyloxycarbamate 571 N-Phenyltrifluoromethanesulfonimide 465 Triethylsilyl Trifluoromethanesulfonate 572 Phthalimidosulfenyl Chloride 469 Trifluoromethanesulfonic Acid 573 Potassium tert-Butoxide–Dimethyl Sulfoxide 471 Trifluoromethanesulfonic Anhydride 581 Potassium Hydroxide–Dimethyl Sulfoxide 474 Trifluoromethanesulfonyl Azide 595 Potassium Monoperoxysulfate 475 Trifluoromethanesulfonyl Chloride 598 Potassium o-Nitrobenzeneperoxysulfonate 487 Trifluoromethanesulfonylmethyl Methyl Sulfone 602 Potassium Nitrosodisulfonate 489 S-(Trifluoromethyl)dibenzothiophenium 1,3-Propanedithiol Bis(p-toluenesulfonate) 491 Triflate 603 N-Propenoyl Camphor-10,2-sultam 493 Trifluoromethyl Phenyl Sulfone 604 3-Propionylthiazolidine-2-thione 495 {[(Trifluoromethyl)sulfonyl]ethynyl}benzene 606 2-Pyridinesulfonyl Chloride 496 (S)-N-Trifluoromethylsulfonyl-2-isopropylaziridine 607 N-(2-Pyridyl)bis(trifluoromethanesulfonimide) 498 [1,1,1-Trifluoro-N- Sodium Dodecyl Sulfate 501 [(trifluoromethyl)sulfonyl]methanesulfonamidato- N-Sulfinyl-p-toluenesulfonamide 503 κN](triphenylphosphine) 610 9-(2-Sulfo)fluorenylmethoxycarbonyl Chloride 505 1,1,1-Trifluoro-N-[(trifluoromethyl)sulfonyl]-N- Sulfonic Acid, Polymer-supported 506 (trimethylsilyl)methanesulfonamide 613 o-Sulfoperbenzoic Acid 515 2,4,6-Triisopropylbenzenesulfonyl Azide 616 Sulfur Trioxide 516 2,4,6-Triisopropylbenzenesulfonyl Hydrazide 623 N,N,N,N-Tetrabromobenzene-1,3-disulfonamide Triisopropylbenzenesulfonyl Tetrazole 629 (TBBDS) 521 Triisopropylsilylethynyl Triflone 632 Tetrachlorothiophene Dioxide 523 Triisopropylsilyl Trifluoromethanesulfonate 633 2,2,4,4-Tetramethylcyclobutan-1-one-3-thione 527 2-Trimethylsilyl-1,3-benzothiazole 635 1,1-(Thiocarbonyl)bis(1H-benzotriazole) 533 [N-(2-(Trimethylsilyl)ethanesulfonyl)imino]phenyliodane 636 2-Thiono-1,3-dioxol-4-ene 535 (Trimethylsilyl)methanesulfonyl Chloride–Cesium Thiophenol–Azobisisobutyronitrile 535 Fluoride 638 Thiophenol, Polymer-supported 536 2-(Trimethylsilyl)phenyl Triflate 639 Thiophosphoryl Chloride 537 Triphenylphosphonium 3,3-Dimethyl-1,2,5- 2-Thiopyridyl Chloroformate 538 thiadiazolidine 1,1-Dioxide 642 Thiourea Dioxide 540 Triphenyl Thioborate 644 p-Toluenesulfinic Acid 541 Trityl Thionitrite 645 p-Toluenesulfonyl Bromide 542 p-Toluenesulfonyl Chloride and Related Reagents, List of Contributors 647 Polymer-supported 545 O-p-Toluenesulfonylhydroxylamine 548 Reagent Formula Index 663 [N-(p-Toluenesulfonyl)imino]phenyliodinane 550 p-Toluenesulfonylmethylene Triphenylphosphorane 553 Subject Index 669 (R)-(+)-p-Tolylsulfinylacetic Acid 555 (R)-(+)-α-(p-Tolylsulfinyl)-N,N-dimethylacetamide 556 General Abbreviations

Preface

The eight-volume Encyclopedia of Reagents for Organic This series has continued over the past several years with the Synthesis (EROS), authored and edited by experts in the field, publication of another series of HROS volumes, each edited by and published in 1995, had the goal of providing an authorita- a current or past member of the e-EROS editorial board: tive multivolume reference work describing the properties and reactions of approximately 3000 reagents. With the coming of Chiral Reagents for Asymmetric Synthesis the Internet age and the continued introduction of new reagents Edited by Leo A. Paquette to the field as well as new uses for old reagents, the electronic sequel, e-EROS, was introduced in 2002 and now contains in Reagents for High-Throughput Solid-Phase and Solution- excess of 4000 reagents, catalysts, and building blocks making Phase Organic Synthesis it an extremely valuable reference work. At the request of the Edited by Peter Wipf community, the second edition of the encyclopedia, EROS II, Reagents for Glycoside, Nucleotide, and Peptide Synthesis was published in March 2009 and contains the entire collection Edited by David Crich of reagents at the time of publication in a 14 volume set. Although the comprehensive nature of EROS and EROS II Reagents for Direct Functionalization of C–H Bonds and the continually expanding e-EROS render them invaluable Edited by Philip L. Fuchs as reference works, their very size limits their practicability in a laboratory environment. For this reason, a series of inexpen- Fluorine-Containing Reagents sive one-volume Handbooks of Reagents for Organic Synthesis Edited by Leo A. Paquette (HROS), each focused on a specific subset of reagents, was introduced by the original editors of EROS in 1999: Catalyst Components for Coupling Reactions Edited by Gary A. Molander Reagents, Auxiliaries, and Catalysts for C–C Bond Formation Reagents for Radical and Radical Ion Chemistry Edited by Robert M. Coates and Scott E. Denmark Edited by David Crich

Oxidizing and Reducing Agents This series now continues with this volume entitled Sulfur- Containing Reagents, edited by Leo Paquette, the originator Edited by Steven D. Burke and Rick L. Danheiser and longtime guiding light of the EROS and HROS volumes, in addition to the online version, e-EROS. This 12th volume in Acidic and Basic Reagents the HROS series, like its predecessors, is intended to be an af- Edited by Hans J. Reich and James H. Rigby fordable, practicable compilation of reagents arranged around a central theme that it is hoped will be found at arm’s reach Activating Agents and Protecting Groups from synthetic chemists worldwide. The reagents have been Edited by Anthony J. Pearson and William R. Roush selected to give broad relevance to the volume, within the limits deﬁned by the subject matter of organosulfur reagents. We have enjoyed putting this volume together and hope that our colleagues will ﬁnd it as much enjoyable and useful to read and consult.

David Crich Centre de Recherche de Gif-sur-Yvette Institut de Chimie des Substances Naturelles Gif-sur-Yvette, France

Introduction

The widespread use of sulfur-containing reagents by syn- The featured reagents have been culled from three sources. thetic chemists is a reflection of the diversity of properties A minority of the entries appeared initially in the Encyclo- offered by this broad class of compounds. The enormous pedia of Reagents for Organic Synthesis (EROS), which was divergence in the reactivity of divalent and tetravalent sulfur published in 1995. Since that time, a significant number of reagents, the stereochemical issues offered by sulfoxides, and entries involving these classical reagents have been updated the ionizability of sulfonic acids represent only a few of the (e-EROS), and this important add-on information is also found many facets of this collective group of reagents. The resulting herein in the form of extensions to the original articles. The demands placed on chemists for the appropriate adaptation of third pool of reagents is constituted of entirely new entries that a given reagent emerge in many forms, not the least of which detail the chemical and physical properties of an added sub- bear on one’s knowledge of reactivity, availability of building set of sulfur-containing compounds. In some instances, groups blocks, appreciation of the consequences of associated changes of reagents coincidentally appear in close proximity, thereby in electronic character, and the like. As a consequence of many facilitating comparative analysis. Subsets consisting of meta- recent developments, it was deemed appropriate to incorporate and para-nitrobenzenesulfonyl peroxide and of β-tosylethyl into a single volume a compilation that brings together a large amine, hydrazine, and hydroxylamine are exemplary. fraction of the more useful organosulfur reagents as well as Among the opening segments of this volume is a section key sulfur-containing promoters that are currently in vogue. that illustrates those procedures relevant to the field that have As usual, the compilation has been arranged alphabetically appeared in volumes 65Ð85 of Organic Syntheses. It is hoped in order to facilitate searching. An added benefit is to foster that these tried and tested protocols will provide a useful level the scanning for information since proximal arrangements by of added guidance in selecting what course of action one might compound type are not prevalent. pursue. All in all, it is hoped that this handbook will prove to be The selection covered in this volume is built on the many a valued adjunct to researchers experienced in sulfur chemistry, important discoveries at the hands of numerous practitioners and a particularly useful compilation for others seeking to gain of our science. These achievements have been realized in con- a foothold in the field as expediently as possible. These goals junction with a very extensive physical organic base. will have been realized if advances materialize from exposure to its contents.

Leo A. Paquette Department of Chemistry The Ohio State University Columbus, OH, USA Short Note on InChIs and InChIKeys

The IUPAC International Chemical Identifier (InChITM) and its we wanted to make sure that all users of e-EROS, the second compressed form, the InChiKey, are strings of letters represent- print edition of EROS and all derivative Handbooks would ing organic chemical structures that allow for structure search- find the same information, we appreciate that the strings will ing with a wide range of online search engines and databases be of little use to the readers of the print editions, unless they such as Google and PubChem. While they are obviously an treat them simply as reminders that e-EROS now offers the important development for online reference works, such as convenience of InChIs and InChIKeys, allowing the online Encyclopedia of Reagents for Organic Reactions (e-EROS), users to make best use of their browsers and perform searches readers of this volume may be surprised to find printed InChi in a wide range of media. and InChIKey information for each of the reagents. If you would like to know more about InChIs and InChIKeys, We introduced InChi and InChIKey to e-EROS in autumn please go to the e-EROS website: www.mrw.interscience. 2009, including the strings in all HTML and PDF files. While wiley.com/eros/ and click on the InChI and InChiKey link. ORGANIC SYNTHESIS PROCEDURES 1

Organic Synthesis Procedures Featuring the Synthesis of Organosulfur Compounds and Preparative Applications thereof, Volumes 65–85

Synthesis of Organosulfur Compounds

N-(4-Acetamidophenylsulfonyl)-2-phenylacetamide 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propyl Propionate S. H. Chol, S. J. Hwang, and S. Chang; Org. Synth. 2008, 85, 131. A. Abiko; Org. Synth. 2003, 19, 109. Ph OH Ph OH MesSO2Cl, Et3N SO2N3 A. CuCN (1.0 mol %) Me NH2 Me NH Et3N (1.1 equiv) + SO2Mes H O, 25 ¡C (–)-Norephedrine 2 2 NHAc NHAc H Ph OH Ph OH N BnCl, Bu4NI S B. K2CO3, CH3CN O O O Me NH Me N Bn

SO2Mes SO2Mes 2 3 Ph O Ph OH Me 2-(4 -Acetylphenyl)thiophene EtCOCl, Py, CH2Cl2 O C. N L. S. Liebeskind and E. Peña-Cabrera; Org. Synth. 2000, 77, 135. Me N Bn Bn SO2Mes SO2Mes (+)-1 3 O Pd/C, CuI − SnBu3 + CH3 ( )-(E,S)-3-(Benzyloxy)-1-butenyl Phenyl Sulfone S AsPh3, NMP, 95 ¡C I O D. Enders, S. Von Berg, and B. Jandeleit; Org. Synth. 2002, 78, 177. S CH3 NH

Cl3CCOBn O c-hexane/CH2Cl2 O H C rt, 48 h, cat TIOH H C A. 3 OEt 3 OEt 1-(Benzenesulfonyl)cyclopentane OH BnO 1 O O H. S. Lin, M. J. Coghlan, and L. A. Paquette; Org. Synth. 1989, DIBAH, Et2O, –78 °C B. H C 1.5 h, then 4 N HCl H C 67, 157. 3 OEt 3 H BnO BnO O CH2Cl2 2 A. PhSO2NHNH2 + PhSeO2H PhSeSO2Ph + N2 + 2H2O O 25 °C (EtO)2PCH2SO2Ph, LiBr H C MeCN, Et3N, 0 °C–rt H C SO C. 3 H 3 2 1. hn, CCl4 B. + PhSeSO2Ph BnO BnO 2. H2O2, CH2Cl2 (S)-3 SO2Ph

Avoid Skin Contact with All Reagents 2 ORGANIC SYNTHESIS PROCEDURES

2,2-Bi-5,6-dihydro-1,3-dithiolo[4,5-b][1,4]dithiinylidene (+)-(2R,8aS)-10-(Camphorylsulfonyl)oxaziridine (BEDT-TTF) J. C. Towson, M. C. Weismiller, G. S. Lal, A. C. Sheppard, and F. J. Larsen and C. Lenoir; Org. Synth. 1995, 72, 265. A. Davis; Org. Synth. 1990, 69, 158.

SH Cl O NEt3/CH2Cl2 S O 0–10 °C A. + SH Cl S A. NH4OH

S O O SO SO SO – + NCS/CCl4 i-PrO S K S SO2Cl SO2NH2 B. reflux acetone/rt S S Cl S S OPr-i

conc H2SO4 0 °C B. H+

S S O N O SO2NH2 SO2 S S

S S S S S S P(OMe)3 C. O Oxone reflux C. S S S S S S K2CO3 N N SO2 SO2 O n-Butyl 4-Chlorophenyl Sulﬁde 2-Chlorophenyl Phosphorodichloridothioate J. C. McWilliams, F. Fleitz, N. Zheng, and J. D. Armstrong III; Org. Synth. 2003, 79, 43. V. T. Ravikumar and B. Ross; Org. Synth. 1999, 76, 271.

OH OSO2CF3 (CF3SO2)2O S A. ONa Cl pyridine, DCM, –10 °C–rt + S PCl O P Cl Cl 3 Cl Cl Cl

OSO2CF3 HS B. Pd(OAc)2, NaHMDS Cl (R)-Tol-BINAP, toluene, 100 °C 4-(3-Cyclohexenyl)-2-phenylthio-1-butene S T. Ishiyama, N. Miyaura, and A. Suzuki; Org. Synth. 1993, 71, Cl 89.

1. Br2 Br A. PhSCH CH2 2. KOH PhS (−)-D-2, 10-Camphorsultam

B M. C. Weismiller, J. C. Towson, and F. A. Davis; Org. Synth. 1990, B. + BH 69, 154.

B Br Pd(PPh3)4 C. + LiAlH4 PhS K3PO4 N H N SPh SO2 SO2

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 3

4,5-Dibenzoyl-1,3-dithiole-1-thione J. Buckley, D. DiBenedetto, and F. A. Davis; Org. Synth. 1995, 93, 159. T. K. Hansen, J. Becher, T. J¿rgensen, K. S. Varma, R. Khedekar, and M. P. Cava; Org. Synth. 1976, 73, 270. O SeO /HOAc Ð + A. 2 S Na Ð + DMF S S Na A. 3CS2 + 3Na S + 2 S N N SÐ Na+ SO2 SO2 S SÐ Na+ 1

S S S S + Ð + O OCH3 1 + ZnCl2 + Et4N Br [Et4N ] S Zn S B. CH(OCH3)3/CH3OH S S S S OCH3 H2SO4/Amberlyst 2 N N SO2 SO2 O S S Ph B. 2 + 4 PhCOCl S Ph Cl S S 1. DBU C. Cl O 2. O 3 N N SO2 Cl NNCl SO2 O Dicyclohexylboron Triﬂuoromethanesulfonate

A. Abiko; Org. Synth. 2003, 78, 103. OCH3 OCH3 D. AcO2H/K2CO3 OCH3 OCH3 Aliquat 336 N N + BH3 á SMe2 BH SO SO O ether 2 2 2 1

BH + CF3SO3H B OSO CF Cl Cl hexane 2 3 AcO H/K CO 2 2 E. Cl 2 2 3 Cl Aliquat 336 N N SO2 SO2 O Diethyl [(Phenylsulfonyl)methyl]phosphonate 2

D. Enders, S. von Berg, and B. Jandeleit; Org. Synth. 2002, 78, 1S-(−)-1,3-Dithiane 1-Oxide 169.

HS Cl S P. C. Bulman Page, J. P. Heer, D. Bethell, E. W. Collington, and (CH2O)n, conc HCl A. D. M. Andrews; Org. Synth. 1999, 76, 37. 1. NaHMDS, THF, 0 °C to rt, 1 h A. SS 2. BuLi, 0 °C to rt, 0.5 h SS O 3. (CH3)3CCO2Et, rt, 2.5 h

Cl S (EtO)2P S P(OEt)3, reflux (CH ) C O B. 3 3

O O OMe (EtO)2P S (EtO)2P SO2 OMe H2O2, AcOH C. B. O N + SS S SS – 1 O2 O

CCl4, 0 °C to rt, 2 d (CH3)3C O (CH3)3C O (+)-(2R,8aR*)-[(8,8-Dimethoxycamphoryl)sulfonyl]oxaziridine and (+)-(2R,8aR*)-[(8,8-Dichlorocamphoryl)- 5% aq NaOH/EtOH sulfonyl]oxaziridine C. SS+ reflux, 24 h SS + O– O– B.-C. Chen, C. K. Murphy, A. Kumar, R. T. Reddy, C. Clark, P. Zhou, B. M. Lewis, D. Gala, I. Mergelsberg, D. Scherer, (CH3)3C O Avoid Skin Contact with All Reagents 4 ORGANIC SYNTHESIS PROCEDURES

Dithieno[3,2-b:2,3-d]thiophene N-Hydroxy-4-(p-chlorophenyl)thiazole-2(3H)-thione

J. Frev, S. Proemmel, M. A. Armitage, and A. B. Holmes; Org. J. Hartung and M. Schwarz; Org. Synth. 2003, 79, 228. Synth. 2006, 83, 209. Br Br Br Br Br 1. BuLi, THF, Ð78 ¡C O 1. Br2, HOAc N A. 2. OHC CHO 2. NH2OH2 á HCl OH S Cl ethanol, water Cl Br S Br N CHO 1 Ð78 to 25 ¡C 2 Br S OEt S Br Br EtO C S S CO Et S HSCH2CO2Et2 2 2 B. N KS OEt N K2CO3, DMF OH acetone OH OHC S CHO S Cl Cl 2 3 S OEt

EtO C S S CO Et S 2 2 1. LiOH, THF, 78 ¡C N ZnCl2 S 2. HCl C. OH Cl S diethyl ether Cl N 3 HO C S S CO H S 2 2 HO

S β-Mercaptopropionitrile (2-Cyanoethanethiol) 4 R. E. Gerber, C. Hasbun, L. G. Dubenko, M. F. King, and D. E. HO C S S CO H S S 2 2 Cu, quinoline Bierer; Org. Synth. 2000, 77, 186. 230 ¡C + Ð S S S NH2 Cl H2O 4 5 A. CN + CN Cl H2N NH2 68Ð100 ¡C H2N S 12then cool 3 Ethynyl p-Tolyl Sulfone + Ð NH2 Cl NaOH CN L. Waykole and L. A. Paquette; Org. Synth. 1989, 67, 149. B. CN HS H2N S distill AlCl3 3 4 A. CH3 SO2Cl + Me3Si C C SiMe3 CH2Cl2 trans-1-(4-Methoxyphenyl)-4-phenyl-3-(phenylthio)azetidin- CH3 SO2 C C SiMe3 2-one

K2CO3, KHCO3 R. L. Danheiser, I. Okamoto, M. D. Lawlor, and T. W. Lee; Org. B. CH3 SO2 C C SiMe3 Synth. 2003, 80, 160. CH3OH, H2O OCH3 OCH CH3 SO2 C HC 3 MgSO4, CH2Cl2 A. PhCHO + N

NH2 CH Fluoromethyl Phenyl Sulfone Ph

1. LiHMDS, THF J. R. McCarthy, D. P. Matthews, and J. P. Paolini; Org. Synth. O CF CO CH CF O B. 3 2 2 3 1995, 72, 209. N2 PhS 2. PhS O C12H25 SO2N3 F SNEt S CH 3 2 S CH F Et3N, H2O, CH3CN 3 (DAST) 2 A. SbCl (cat) cat Rh (OAc) 3 OCH3 O 2 4 + CH2Cl2 1 C. N2 PhS N OCH3 S CH2F Oxone¨ SO2CH2F CH B. Ph O N 1 2 PhS Ph

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 5

Methyl (Z)-3-(Benzenesulfonyl)prop-2-enoate (S)-(−)-Methyl p-Tolyl Sulfoxide

G. C. Hirst and P. J. Parsons; Org. Synth. 1990, 69, 169. S. H. Zhao. O. Samuel, and H. B. Kagan; Org. Synth. 1990, 68, 49. H3BO3 THF/H2O Ti(Oi-Pr) HC COOCH +CH SO Na 4 3 6 5 2 C H SO COOCH CH3 SCH3 Bu4NHSO4 6 5 2 3 diethyl (2S,3S)-tartrate 80% cumene hydroperoxide H2O, CH2Cl2 O

CH3 S CH 2-Methylene-1,3-dithiolane 3

K. R. Dahnke and L. A. Paquette; Org. Synth. 1993, 71, 175.

S SH HCl (conc) A. ClCH2CH(OMe)2 + Cl 2-(Phenylsulfonyl)-1,3-cyclohexadiene HS 0Ð25 ¡C S H J.-E. Bäckvall, S. K. Juntunen, and O. S. Andell; Org. Synth. 1990, 68, 148. S S Et2O B. Cl + MeLi á LiBr 0Ð25 ¡C H PhSO2Na, HgCl2 S S HgCl DMSO/H2O, 1/5 rt SO2Ph

S-Methyl Methanethiosulfonate 2 M NaOH (aq) HgCl Et2O or CH2Cl2 F. Chemla and P. Karoyan; Org. Synth. 2002, 78, 99. rt SO2Ph SO2Ph O O Zn powder, CH3COCl 3 SCH Cl 3 SCH S CH3 ethyl acetate O O

Phenylthioacetylene P. A. Magriotis and J. T. Brown; Org. Synth. 1995, 72, 252. (Rs)-(+)-2-Methyl-2-propanesulﬁnamide 1. Br (1.0 equiv) 2 PhS CH2Cl2, 0 ¡C D. J. Weix and J. A. Ellman; Org. Synth. 2005, 82, 157. A. PhS 2. 40% aq NaOH Br CH2Cl2, 23 ¡C + Ð Bu4N HSO4 5 mol % OH O PhS NaNH2 (2.1 equiv) B. PhS OH EtOH N OH liq NH , Et O A. + Br 3 2

NH2 OH

ligand (Phenylthio)nitromethane ligand, VO(acac)2 O S acetone, 0 °C S A. G. M. Barrett, D. Dhanak, G. G. Graboski, and S. J. Taylor; B. S S 30% H2O2 (aq) Org. Synth. 1990, 68,8.

SO2Cl2 O 1. LiNH , NH , THF O A. PhSH PhSCl 2 3 Et3N Fe(NO ) · 9H O C. S 3 3 2 S S NH2 2. ice, ClCH2CO2H NaCH2NO2 B. PhSCl PhSCH2NO2 EtOH

Avoid Skin Contact with All Reagents 6 ORGANIC SYNTHESIS PROCEDURES

Phenyl Vinyl Sulﬁde 1,4,8,11-Tetrathiacyclotetradecane D. S. Reno and R. J. Pariz; Org. Synth. 1997, 74, 124. J. Buter and R. M. Kellogg; Org. Synth. 1987, 65, 150.

Br2, C2H4, CH2Cl2 S S Br S S NaOEt/EtOH S A. + HS SH 2 Cl OH OH HO DBU

Br S S S 1. conc HCl S S 2. KOH/H2O S S B. + 2 H2N NH2 3. HCl/H2O OH HO SH HS N-(2-Pyridyl)triﬂimide and N-(5-Chloro-2-pyridyl)triﬂimide S S D. L. Comins, A. Dehghani, C. J. Foti, and S. P. Joseph; Org. S S 2Cs2CO3 C. + Br Br Synth. 1997, 74, 77. DMF 55Ð60 ¡C S S SH HS 1. pyridine

2. (Tf)2O Tf N NH2 N N 9-Thiabicyclo[3.3.1]nonane-2,6-dione Tf 1 R. Bishop; Org. Synth. 1992, 70, 120. Cl Cl 1. pyridine Cl 2. (Tf)2O Tf A. SCl + N NH2 N N 2 Cl Tf S 2 1

Cl OH

Na2CO3

B. H2O 2,3,3α,4-Tetrahydro-2-[(4-methylbenzene) Cl OH S S sulfonyl]cyclopenta[c]pyrrol-5(1H)-one 2

OH M. C. Patel, T. Livinghouse, and B. L. Pagenkopf; Org. Synth. O (COCl)2 2003, 80, 93. C. CH3SOCH3 OH H S S TsCl, pyridine A. H2NTsN 3 O 10 °C 1 2 N-p-Tolylsulfonyl-(E)-1-Phenylethylideneimine H K2CO3, acetone B. TsN TsN C3H3Br, reflux J. L. G. Ruano, J. Aleman, A. Parra, and M. B. Cid; Org. Synth. 2 3 2007, 84, 129.

O (OC)3Co SOp-Tol HO HO O N CO2(CO)8 Ph C. A. Tol S NH Me H Me Co(CO)3 2 Ti(OEt) Et2O 4 Ph Me Me Me CH Cl , reflux 4 5 1 2 2 2

(OC) Co SOp-Tol SO p-Tol 3 N N 2 HO m-CPBA 1. Et3SiH, CycNH2 B. D. Me Co(CO)3 TsN O 2. 3, 1,2-DME Ph Me CH2Cl2 Ph Me Me 5 67 °C 6 2 3

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 7

α-Tosylbenzyl Isocyanide (S)-(+)-2,4,6-Trimethylbenzenesulﬁnamide

J. Sisko, M. Mellinger, P. W. Sheldrake, and Neil H. Baine; Org. T. Ramachandar, Y. Wu, J. Zhang, and F. A. Davis; Org. Synth. Synth. 2000, 77, 198. 2006, 83, 131.

NH2 O O HCl S A. Cl Na2CO3/H2O O A. OH + S EtOAc/THF O rt/7 h NH SO2Na á xH2O SO2H 92% 1 OH TolSO 2 1 CHO CHO H2NCHO N B. + H TMSCl 2 SO2H O O S SOCl2 S 1 B. O NH 3,5-lutidine O N O THF, Ð45 ¡C S TolSO2 TolSO2 16 h 81% O CHO OH N POCl3 N C C. H 1 2 Et3N 2 3

O O MesMgBr (1.1 equiv) S C. S O N O THF, Ð78 ¡C O NH trans-4,7,7-Tricarbomethoxy-2- S 3 h O phenylsulfonylbicyclo[3.3.0]oct-1-ene O S O A. Padwa, S. H. Watterson, and Z. Ni; Org. Synth. 1997, 74, 147. 2 3 SOPh PhSCl CH A. HOCH2 C C CH2OH 2 NEt CH2 O Li/NH3/Fe(NO3)3 á 9H2O 3 D. S SOPh O THF, Ð78 ¡C NH 4 h O SOPh SO2Ph S H2O2 O B. CH2 CH2 CH2 AcOH CH2 O SOPh SO2Ph 3 O 1 + S S H2N O 1. NaH NH C. CH2(CO2CH3)2 2. CH3OOC Br 4 58% OH CH OOC CH(CO CH ) 3 2 3 2 1 quant

1. NaH 2-Trimethylsilylethanesulfonyl Chloride D. CH3OOC CH(CO2CH3)2 2. SO2Ph CH S. M. Weinreb, C. E. Chase, P. Wipf, and S. Venkatraman; Org. 2 CH 2 Synth. 1998, 75, 161. SO2Ph NaHSO3 SO Ph PhCO3t-Bu 2 A. SO3Na Me3Si Me3Si CO CH aq MeOH 2 3 50 ¡C 1 CO CH 2 3 SOCl2 SO Na cat DMF CO2CH3 B. 3 SO2Cl Me3Si 0 ¡CÐrt Me3Si 1 2

Avoid Skin Contact with All Reagents 8 ORGANIC SYNTHESIS PROCEDURES Synthetic Applications of Sulfur-Containing Compounds

4-Acetoxyazetidin-2-one Allylcarbamates by the Aza-ene Reaction: Methyl N-(2- methyl-2-butenyl)carbamate S. J. Mickel, C.-N. Hsiao, and M. J. Miller; Org. Synth. 1987, 65, 135. G. Kresze, H. Braxmeier, and H. Münsterer; Org. Synth. 1987, 65,

2C CHH 159. OAc OAc OAc + 2Cl2/AcOH/H2O N NH A. H2NCO2Me Cl2NCO2Me CO NSO2Cl O SO2Cl O

SCl2/pyridine B. 2 Cl2NCO2Me MeO2CN S NCO2Me 2-(N-Acetylamino)-4,4-dimethoxy-1,1,1-triﬂuorobutane

F. Gagosz and S. Z. Zard; Org. Synth. 2007, 84, 32. 1. NHCO Me C. MeO2CN S NCO2Me 2 2. KOH/MeOH OMe AcNH NHAc A. 2 F COH 1,4-dioxane F COH 3 reflux 3 1

NHAc SOCl NHAc B. 2 F COH heptane F CCl Asymmetric Synthesis of Methyl (R)-(+)-β-Phenylalanate 3 85 ¡C 3 1 2 from (S)-(+)N-(Benzylidene)-p-toluenesulﬁnamide S NHAc AcHN O EtO SÐ,K+ D. L. Fanelli, J. M. Szewczyk, Y. Zhang, G. V. Reddy, D. M. C. F CCl ethanol F CSOEt Burns, and F. A. Davis; Org. Synth. 2000, 77, 50. 3 25 ¡C 3 2 3 S Me

AcHN O O O OAc AcHN O OEt D. S LiHMDS S F CSOEt lauroyl peroxide O –78 °C to rt NH2 3 1,2-dichloroethane F3C OAc A. 3 reflux 4 Me MeMe Me S 1 2

AcHN O OEt MeOH, reflux AcHN O E. F C OAc camphorsulfonic F C O O O 3 acid 3 4 S S 5 NH PhCHO N Ph B. 2 Ti(OEt)4 3-Acetyl-4-hydroxy-5,5-dimethylfuran-2(5H)-one Me Me 2 3

C. M. J. Fox and S. V. Ley; Org. Synth. 1988, 66, 108. O – + A. (CH3)3CSH + NaH (CH3)3CS Na S N Ph NaHMDS/CH3CO2Me CH2 C. OO –78 °C – + Me (CH3)3CS Na + O (CH ) CS 3 O O 3 3 S NH OO OH AgOCOCF3 CO Me B. + Me Ph 2 CO Me (CH3)3CS 2 OO 4

MeO2C O O NH S 2 O NH TFA/MeOH CO2Me OO – – HO D. Ph Bu3N F CO Me C. Me Ph 2 5 MeO2C O 4 O O

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 9

2-O-Benzyl-3,4-isopropylidene-D-erythrose Chiral 1,3-Oxathiane from (+)-Pulegone: Hexahydro-4,4,7- Trimethyl-4H-1,3-benzoxathiin A. Dondoni and P. Merino; Org. Synth. 1995, 72, 21.

N 1. BuLi N E. L. Eliel, J. E. Lynch, F. Kume, and S. V.Frye; Org. Synth. 1987, A. 65, 215. S Br 2. Me3SiCl S SiMe3 2-TST SCH C H 2-TST 2 6 5 B. O O S O O O O NaOH CHO N A. + C6H5CH2SH THF OH reflux

O O S S NaH, C6H5CH2Br O C. O SCH2C6H5 SH N N O OH OH OCH C H Na, NH3 2 6 5 B. CH3OH Ð78 ¡C O S 1. Mel O D. O O CHO N 2. NaBH4 3. HgCl2, H2O SH S OCH2C6H5 OCH2C6H5 H OH O N-(Benzyloxycarbonyl)-L-vinylglycine Methyl Ester (CH2O)n C. H p-CH3C6H4SO3H M. Carrasco, R. J. Jones, S. Kamel, H. Rapoport; Org. Synth. 1992, C6H5 70, 29. reflux

CO2CH3 CO2CH3 CbzCl A. + Ð K2CO3 S NHCbz S NH2 Cl 1 2

CO2CH3 CO2CH3 NaIO B. 4 S NHCbz S NHCbz Cholesta-3,5-diene 2 3 O

CO2CH3 CO2CH3 S. Cacchi, E. Morera, and G. Ortar; Org. Synth. 1990, 68, Δ 138. C. S NHCbz NHCbz 3 4 O (S)-2-[(4S)-N-tert-Butoxycarbonyl-2,2-dimethyl-1,3- oxazolidinyl]-2-tert-butyldimethylsiloxyethanal (CF3SO2)2O A. A. Dondoni and D. Perrone; Org. Synth. 2000, 77, 78. Me N NBoc O NBoc S SiMe3 O S t-Bu N t-Bu A. O CHO N 1 OH 2

NBoc NBoc S TBDMSOTf S B. O O CF3SO2O N N 1 OH OTBDMS 2 3

NBoc NBoc S 1. MeOTf Pd(OAc)2, Ph3P C. O O B. 1 n-Bu N, HCOOH 2. NaBH4 CHO 3 N 3. CuO, CuCl2, H2O OTBDMS OTBDMS 3 4

Avoid Skin Contact with All Reagents 10 ORGANIC SYNTHESIS PROCEDURES

Dec-9-enyl Bromide from 10-Undecenoic Acid (2S,3S)-Dihydroxy-1,4-diphenylbutane

D. H. R. Barton, J. MacKinnon, R. N. Perchel, and C.-L. Tse; Org. M. A. Robbins, P. N. Devine, and T. Oh; Org. Synth. 1999, 76, Synth. 1998, 75, 124. 101.

O DCC + OH CH2Cl2, 0 ¡C HOCH2 S N O CH3SO3CH2 CH2SO3CH3 1. CH3SO2Cl, pyr OH A. O 2. CH3SO3H 1 2 HOCH2 EtOH, H2O HO OH O BrCCl3 Br CH SO CH O hν 3 3 2 CH2SO3CH3 KOH B. O O N S EtOHÐH O HO OH 2

3 4 HO 1. PhMgBr, CuI OH C. O O + Ð 3-Deoxy-1,2:5,6-bis-O-(1-methylethylidene)-α-D-ribo- 2. NH4 Cl BnBn hexofuranose

J. Tormo and G. C. Fu; Org. Synth. 2002, 78, 239.

Me Me O S O pyridine 1,2-Dimethylenecyclohexane A. O O + CH2Cl2 H Me Cl OPh rt E. Block and M. Aslam; Org. Synth. 1987, 65, 90. HO O Me Me Me O O O O H S S Me H2O A. + 9Br2 3BrCH2SO2Br O O Me SS PhO 1 Br Me BrCH2SO2Br KOt-Bu Me B. O 7.5% (Bu3Sn)2O hν O PHMS SO2CH2Br B. O O H H AIBN S Me BuOH benzene, Δ O O Me PhO 1 Me Me O O O O H Me 2,4-endo,endo-Dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one O Me 2 M. Lautens and G. Bouchain; Org. Synth. 2003, 79, 251.

(E)-1-Diazo-4-phenyl-3-buten-2-one

R. L. Danheiser, R. F. Miller, and R. G. Brisbois; Org. Synth. 1995, O O CCl4 73, 134. A. + SO2Cl2 45 °C Cl 1 2 O 1. LiHMDS, THF CF3CO2CH2CF3 O

2. C12H25 SO2N3, Et3N O O Et3N H2O, CH3CN O B. + O H2O, rt N2 Cl 2 3

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 11

(2S,3R)-2,4-Dimethyl-1,3-pentanediol Ethyl 2-{[(1S,2R,3R,5S-2,6,6-Trimethylbicyclo[3.1.1]hept-3- yl]methyl}acrylate A. Abiko; Org. Synth. 2003, 79, 116. Ph O Ph O OH V. Darmency, E. M. Scanlan, A. P. Schaffner, and P. Renaud; Org. 1. cHex2BOTf, Et3N Me CH2Cl2 Me Synth. 2006, 83, 24. A. O O 2. i-PrCHO N 3. 30% H2O2 N Bn SO2Mes pH 7 bufferÐMeOH Bn SO2Mes CO2Et CO2Et (+)-1 2 1. I2, NaSO2Ph, EtOH, 0 ¡C A. SO Ph 2. Et3N, CH2Cl2, rt 2 Ph O OH 1

Me 1. LiAlH4, THF B. O 2. Na2SO4 á H2O N 1. CatBH, MeCONMe2 (10 mol %) Bn SO Mes CH2Cl2 COOEt 2 Ph B. OH CO Et 2 Me 2. O2, 2 + OH SO2Ph HO 2 N Bn SO2Mes 3 4

GlcNAc-thiazoline Triacetate 9-Dithiolanobicyclo[3.2.2]non-6-en-2-one S. Knapp, R. A. Huhn, and B. Amorelli; Org. Synth. 2007, 84, 68. K. R. Dahnke and L. A. Paquette; Org. Synth. 1993, 71, 181.

HO O Ac2O A. HO O HO OH montmorillonite K-10 NHAc AcO SeO2 A. O KH PO AcO 2 4 OAc dioxane, H2O AcO 90 ¡C NHAc O O OAc S O (C2H5)3N AcO B. + AcO 110Ð120 ¡C O P4S10, i-PrOAc AcO S S B. AcO S AcO OAc Me3SiOSiMe3 N NHAc S O O H3C

CH3Li, CuI C. S (i-Bu)2AlH S THFÐHMPA S Ð50 to 0 ¡C S 2-Hexyl-5-phenyl-1-penten-3-ol

K. Takai, K. Sakogawa, Y. Kataoka, K. Oshima, and K. Utimoto; 4-Dodecylbenzenesulfonyl Azides Org. Synth. 1995, 72, 180.

G. G. Hazen, F. W. Bollinger, F. E. Roberts, W. K. Russ, J. J. Seman, and S. Staskiewicz; Org. Synth. 1995, 73, 144. TtOH A. hexane, Ð30 to 0 ¡C OTf

C12H25 C12H25 SOCl2/DMF Ph CrCl2, cat NiCl2 hexane B. OTf + OHC SO3H SO2Cl DMF, Ð25 ¡C

C12H25 NaN3, H2O Ph Aliquat 336 SO2N3 OH

Avoid Skin Contact with All Reagents 12 ORGANIC SYNTHESIS PROCEDURES

3-Hydroxy-1-cyclohexene-1-carboxaldehyde N-(4-Methoxybenzyl)-3-phenylpropylamine

H. L. Rigby, M. Neveu, D. Pauley, B. C. Ranu, and T. Hudlicky; W. Kurosawa, T. Kan, and T. Fukuyama; Org. Synth. 2003, 79, Org. Synth. 1989, 67, 205. 186. SO2Cl A. NO2 NH NEt3 2 + CH Cl S 2 2 O CHO MeO HO S dithiane, BuLi HgO, BF á Et O 3 2 NO2 THF H2O, THF SO OH N 2 1 2 3 H MeO

1-Hydroxy-3-phenyl-2-propanone NO2 Ph(CH ) Br SO2 2 3 N K2CO3 M. S. Waters, K. Snelgrove, and P. Maligres; Org. Synth. 2003, B. H 80, 190. DMF MeO 60 ¡C

NO2

SO2 PrSH, KOH (aq) OH N A. MeCN SPr OH MeO 1 2

OH H2SO4 OH B. SPr EtOH/H2O O NO2 2 3 SO2 N PhSH, KOH C. CH3CN MeO 50 ¡C

NH Mesitylenesulfonylhydrazine, and (1α,2α,6β)-2,6-Dimethylcyclohexanecarbonitrile and MeO (1α,2β,6α)-2,6-Dimethylcyclohexanecarbonitrile as a Racemic Mixture

J. R. Reid, R. F. Dufresne, and J. J. Chapman; Org. Synth. 1997, 74, 217. 5-Methyl-2,2-bipyridine

A. P. Smith, S. A. Savage, J. C. Love, and C. L. Fraser; Org. Synth. 2002, 78, 51. H SO , H O SO2Cl SO2NHNH2 2 4 2 ClSO3H N2H4 A. A. NaNO2 N NH2 N OH 1 1

(CF3SO2)2O O SO2NHNH2 B. 25 ¡C B. + pyridine 14 h NOH NOSO2CF3 1 2

CN 1. t-BuLi, THF N KCN, CH3CN 2. ZnCl2 NNHSO C. 2 3. 2, LiCl, THF reflux, 7 h N NBr Pd(PPh3)4 2 3

A list of General Abbreviations appears on the front Endpapers ORGANIC SYNTHESIS PROCEDURES 13

2-Methyl-4-[(phenylsulfonyl)methyl]furan and 3-Morpholino-2-phenylthioacrylic Acid Morpholide and 2-Methyl-3-[(phenylsulfonyl)methyl]-2-cyclopenten-1-one 5-(4-Bromobenzolyl-2-(4-morpholino)-3-phenylthiophene

S. H. Watterson, Z. Ni, S. S. Murphree, and A. Padwa; Org. Synth. A. Rolfs and J. Liebscher; Org. Synth. 1997, 74, 257. 1997, 74, 115. Ph S

SO Ph S /HN O 1. PhSCl, Et3N 2 O N A. H CH2OH CH2 CC 2. H2O2, HOAc H A. Ph CH3 O Br Ph Ph SO Ph 2 Br2 Br H B. CH2 CC S S H HOAc SO2Ph N HC(OEt)3 /HN O N N B. O O Br CH2SO2Ph O O O C. Br H Ph CH3ONa, CH3OH S Ph CH3 SO2Ph O O O N N Br O O Br ON C. S O Br O O CH3 D. Br H CH3 CH ONa, CH OH 3 3 Br SO2Ph CH2SO2Ph (E)-1-Phenyl-3,3-dimethyl-1-butene

T.-M. Yuan and T.-Y. Luh; Org. Synth. 1997, 74, 187. Methyl (S)-2-Phthalimido-4-oxobutanoate O SS BF3 á OEt2 A. + HSCH2CH2SH P. Meffre, P. Durand, and F. Le Goffic; Org. Synth. 1999, 76, 123. Ph Me Ph Me B. MeI + Mg MeMgI O SS MeMe O NiCl2(dppp) C. Ph Me + MeMgI Ph Me O A. CH3S CO2CH3 CH3S CO2CH3 NEt3, toluene + Ð 4S-4-(2-Phenylethyl)-2-oxetanone NH3 Cl NPhth S. G. Nelson and P. M. Mills; Org. Synth. 2005, 82, 170. SO CF CH S 1. NCS, CCl4 H CO CH 2 3 B. 3 CO2CH3 2 3 H2N OH (CF3SO2)2O, Et3N N 2. H2O A. NPhth O NPhth CH2Cl2, Ð78 ¡C i-Pr i-Pr 1 Bn SO2CF3 i-Pr i-Pr N BnNH2 N B. Mild and Selective Oxidation of Sulfur Compounds in 100 ¡C NH HN i-Pr F CO S SO CF Trifluoroethanol: Diphenyl Disulfide and Methyl Phenyl 1 3 2 2 2 3 Sulfoxide Bn i-Pr i-Pr N Me3Al K. S. Ravikumar, V. Kesavan, B. Crousse, D. Bonnet-Delpon, and C. NH HN CH2Cl2 J.-P. Begue; Org. Synth. 2003, 80, 184. F3CO2S SO2CF3 2 Bn i-Pr i-Pr N SH 1.1 equiv 30% H2O2 N Al N S S F CO S SO CF trifluoroethanol 3 2 Me 2 3 3 O O S 1.1 equiv 30% H O S O O O CH3 2 2 CH3 10 mol % 3 D. + trifluoroethanol i-Pr2NEt, CH2Cl2 Me Br H Ph Ð50 ¡C Ph

Avoid Skin Contact with All Reagents 14 ORGANIC SYNTHESIS PROCEDURES

2-Propyl-1-azacycloheptane from Cyclohexanone Oxime Triethyl 1,2,4-triazine-3,5,6-tricarboxylate

K. Maruoka, S. Nakai, and H. Yamamoto; Org. Synth. 1988, 66, D. L. Boger, J. S. Panek, and M. Yasuda; Org. Synth. 1988, 66, 185. 142.

Et2NH H2NCO2Et OH OSO2CH3 A. CN CO Et N N 2 H2S S

CH3SO2Cl A. NEt2 H NCOEt H NCOEt 2 2 N2H4 2 2 CH2Cl2 B. S N OSO2CH3 H2N N H HO OH EtO2CO N Pr N Pr HCl(g) C. NaO2C Pr3Al i-Bu2AlH CO2Na C2H5OH, 0 ¡C B. HO OH EtO2C O CH2Cl2 hexane hexane EtO COH NCOEt EtO CNCO Et D. 2 2 2 2 2 + N 25 ¡C N EtO C O EtO C N 2 H2N 2 (+)-(1R,2S,3R)-Tetracarbonyl[(1-3η)-1-(phenylsulfonyl)but- 2-en-1-yl]iron(1+) Tetraﬂuoroborate EtO2CNCO2Et EtO2CNCO2Et E. + N D. Enders, B. Jandeleit, and S. von Berg; Org. Synth. 2002, 78, N O 189. EtO2C N EtO2C

1. Fe2(CO)9, n-hexane or pentane, 3 d, rt (E,E)-Trimethyl(4-phenyl-1,3-butadienyl)silane H C SO Ph 2. extract, crystallization H C SO Ph A. 3 2 3 2 Z. J. Ni and T.-Y. Luh; Org. Synth. 1992, 70, 240. BnO BnO Fe(CO)4 S CHO BF3 á OEt2 A. Ph + HSCH2CH2SH Ph S

H C SO Ph HBF4, Et2O, 30 °C, 2 h H CSOPh B. Me SiCH Cl Mg Me SiCH MgCl B. 3 2 3 2 3 2 + 3 2 BnO Fe(CO) Fe(CO) 4 4 S BF4 NiCl2(PPh3)2 C. + Me3SiCH2MgCl (1R,2S,3R)-1 Ph S SiMe Ph 2

A list of General Abbreviations appears on the front Endpapers ALLYL TRIFLONE 15

Creary reported the synthesis of allyl triﬂone in moderate yield by reacting allylmagnesium chloride with triﬂic anhydride (eq 3).3

O ether, −78 °C + (CF3SO2)2O S CF MgCl 54% 3 (3) O A 5

Allyl Triflone Hendrickson synthesized allyl triflones using tetrabutylammonium triflinate.4 The quaternary ammonium system is more soluble and 20Ð40 times more reactive than the conventional SO2CF3 potassium triflinate. Tetra-n-butylammonium azide (6) prepared from tetra-n-butylammonium hydroxide and sodium azide reacts with triflic anhydride in chloroform at −78 ◦Ctogivea1:1 [73587-48-1] C4H5F3O2S (MW 174.14) InChI = 1/C4H5F3O2S/c1-2-3-10(8,9)4(5,6)7/h2H,1,3H2 mixture of tetrabutylammonium triflinate (7) and tetrabutyl- InChIKey = QPPGNZFPJHEEHR-UHFFFAOYAB ammonium triflate (8). Treatment of this mixture with allyl bromide gives the corresponding allyl triflone (5) in almost quanti- (allylating agent) tative yield. The water-soluble triflate coproduct (8) in the reaction mixture does not interfere with the formation of (5), which is read- Alternate Names: 3-(trifluoromethylsulfonyl)prop-1-ene; allyl ily isolated (eq 4). trifluoromethyl sulfone. ◦ Physical Data: bp 171.5 C. − ° NaN3 + − (CF3SO2)2O CHCl3, 78 C Form Supplied in: colorless liquid; not commercially available. n-Bu4NOH n-Bu4N N3 Handling, Storage, and Precautions: moisture sensitive; ther- 6 mally labile. + − + − n-Bu4N CF3SOO + n-Bu4N CF3SO2O 7 8 Free-radical allylations are powerful tools for the selective formation of carbon-carbon bonds under mild conditions. These ° transformations have been accomplished by reacting alkyl halides allyl bromide, 50 C, 10 h 98% with allyl stannanes, allyl silanes, allyl sulfones, the title compound allyl trifluoromethanesulfone (allyl triflone), and its substi- O (4) tuted derivatives. The strong electron withdrawing ability of the SCF3 trifluoromethylsulfone group in allyl triflones facilitates the addi- O tion of an alkyl radical to an electron deficient triflone. The use of 5 allyl triflones, together with other reagents such as allyl sulfones, avoids the toxicity and difficulty in removing tin residues from the products associated with stannane reagents. Synthesis of Functionalized Allyl Triflones. The Hendrick- son tetrabutylammonium triflinate reagent (7/8)4 reported was Synthesis of Allyl Triflone. Alkyl triflones are formed in a used by Fuchs and Curran to prepare functionalized allyl triflones 5 clean, but slow, displacement reaction by nucleophilic substitution (9Ð13). of primary halides by potassium triflinate with iodide catalysis in boiling acetonitrile (eq 1).1 CO2Me CO2Et CN

KI, acetonitrile reflux SO2CF3 SO2CF3 SO CF RCH2Br + KSO2CF3 RCH2SO2CF3 (1) 2 3 9 1 23 10 11 [210489-89-7] [210489-88-6] [210489-90-0] An alternative synthesis of allyl triflones is the triflination of allyl alcohols, which affords triflinates such as 4, followed by ther- Ph n-C8H17 mal rearrangement in acetonitrile to give allyl triflone (5) (eq 2).2 SO2CF3 SO2CF3 pyridine, acetonitrile, rt OH + CF3SOCl 68% 12 13 [210489-91-1] [210489-92-2]

O O acetonitrile, 120 °C Fuchs and co-workers used radical-mediated atom-transfer OSCF3 SCF3 (2) 85% addition of iodomethyl triﬂone (14) [158530-86-0] to substituted 4 O alkynes to afford functionalized allyl triﬂones.6 The reaction was 5 complete within 5Ð10 h in most cases. For example, heating a

Avoid Skin Contact with All Reagents 16 AMINOIMINOMETHANESULFONIC ACID benzene solution of iodomethyl triﬂone (14) (1 equiv) and alkyne R R 0.05 equiv AIBN 0.05 equiv AIBN (2Ð3 equiv, to ensure an excess of the volatile substrate) in a sealed cyclohexane, reflux THF, reflux SO2CF3 tube gave allyl triﬂone (15) in 99% yield (eq 5). The procedure 70~90% 70~90% was also extended to internal and terminal alkynes. Addition to 9aÐ13a 9Ð13 1-octyne and 4-octyne proceeded in over 70% yield, but resulted in a mixture of E- and Z-isomers. R (8) O O O S 0.05 equiv Bz2O2 or AIBN R = CO2Me, CO2Et, CN, Ph, n-C8H17 I + TMS H 9bÐ13b F3C benzene, 100 °C 99% 14 TMS H (5)

I SO2CF3 1. Hendrickson, J. B.; Giga, A.; Wareing, J., J. Am. Chem. Soc. 1974, 96, 15 2275. Z: [162052-46-2] 2. Hendrickson, J. B.; Skipper, P. L., Tetrahedron 1976, 32, 1627. (E:Z=1:7.5) E: [162052-45-1] 3. Creary, X., J. Org. Chem. 1980, 45, 2727. 4. Hendrickson, J. B.; Judelson, D. A.; Chancellor, T., Synthesis 1984, 17. 5. Xiang, J.; Evarts, J.; Rivkin, A.; Curran, D. P.; Fuchs, P. L., Tetrahedron Fuchs also reported the preparation of allyl triflones through Lett. 1998, 39, 4163. 1,2-elimination of the γ-iodoso triflone intermediate. γ-Iodoso 6. Mahadevan, A.; Fuchs, P. L., J. Am. Chem. Soc. 1995, 117, 3272. triflone was prepared from γ-iodo triflones using dimethyldioxi- 7. Ek, F.; Wistrand, L.; Frejd, T., J. Org. Chem. 2003, 68, 1911. rane. In all of the cases, the elimination gave the corresponding 6 allyl triflones regio- and stereoselectively (eq 6). Formation of Jason Xiang & Yonghan Hu allyl triflone (17) demonstrates that the triflone moiety is more Wyeth Research, Cambridge, MA, USA inductively activating than the phenyl ring in substrate 16.

I Ph dimethyldioxirane Aminoiminomethanesulfonic Acid SO2CF3 93% 16 SO3H Ph SO CF HN NH 2 3 (6) 2 17 [162052-52-0] [1184-90-3] CH4N2O3S (MW 124.13) InChI = 1/CH4N2O3S/c2-1(3)7(4,5)6/h(H3,2,3)(H,4,5,6)/ f/h2,4H,3H2 InChIKey = AOPRFYAPABFRPU-VAGMHOQLCM Allyl Triflone as an Allylating Agent. Frejd reported a low yield method using allyl triflone for aromatic allylation through a (parent compound and its derivatives guanylate amines; some diazotization/allylation process (eq 7).7 derivatives give triazoles with azide and aminoiminoethane- nitriles with cyanide as nucleophile) Alternate Name: formamidinesulfonic acid. NH 2 O Physical Data: mp 131Ð131.5 ◦C when highly pure; around tert-butyl nitrite, acetonitrile ◦ SCF3 125 C with dec before purification. + 29% O Solubility: sol water; slightly sol methanol, ethanol; insol ether. O2N NO2 5 Preparative Methods: by the oxidation of thiourea or amino- iminomethanesulfinic acid (formamidinesulfinic acid) with peracetic acid. Many substituted aminoiminomethanesulfonic (7) acids can be prepared in the same way.1,2 Others have utilized hydrogen peroxide with sodium molybdate as a catalyst to oxidize the corresponding thioureas to a vari-

O2N NO2 ety of monosubstituted aminoiminomethanesulfonic acids; the substituents include phenyl, 2-methylphenyl, 4-fluorophenyl, n-propyl,3 cyclohexylmethyl, S-α-methylbenzyl, cyclooctyl, Curran and Fuchs successfully reacted allyl triflones with THF and benzhydryl.4 and cyclohexane to give good to excellent yields of various allyl Purification: recrystallize from glacial acetic acid. products through radical-mediated CÐH bond functionalization Handling, Storage, and Precautions: stable for at least a few (eq 8).5 weeks at room temperature. After drying, it remains stable for

A list of General Abbreviations appears on the front Endpapers AMINOIMINOMETHANESULFONIC ACID 17

at least 5 months if kept in a freezer. Thiourea and its metabo- In contrast, both (3R)- and (3S)-hydroxy-L-arginine have been pre- lites (probably oxidized thiourea) are tumorigenic and cause pared by guanylation of the tridentate copper complexes of threo- 8 lung edema. All direct contact with the compound should be and erythro-2-hydroxy-L-ornithine using S-methylisothiourea. avoided; for example, a dust mask should be worn. All residues Aminoiminomethanesulfonic acid has been used in the synthe- should be destroyed with strong bleach solution. Many sub- sis of an α-hydroxy ester C-terminal homo-L-arginine tripeptide stituted thioureas and their metabolites are also biologically for evaluation as a thrombin inhibitor.9 The synthesis of a par- active. Use in a fume hood. tially modiﬁed retroÐinverso T-cell epitope analog required preparation of the malonylarginine intermediate (2) using aminoiminomethanesulfonic acid as the guanylating agent (eq 3).10 Synthesis of Guanidines from Amines. Aminoimino- methanesulfonic acid (1) reacts with a variety of primary amines, EtO2C CO2-t-Bu 1. H2/PdÐC, MeOHÐAcOH, 12 h including tert-butylamine, to give 50Ð80% yields of the corre- 2. (1), 10% aq. Na2CO3, 72 h, rt sponding guanidines (eq 1). This reaction is more facile than guanidine syntheses starting with S-alkylisothioureas.2 Reac- 3. MtrCl, 4N NaOH, acetone, 2 h tions of primary and secondary amines with monosubstituted NHCbz EtO2C CO2-t-Bu (phenylamino)- and (n-propylamino)iminomethanesulfonic acids also give good to excellent yields of the corresponding guani- NH (3) dines. Treatment of (n-propylamino)iminomethanesulfonic acid (2) N NHMtr with a hindered amine, t-butylamine, leads to a good yield of the H corresponding triazine instead of the guanidine.3 Mtr = 2,3,6-trimethyl-4-methoxybenzenesulfonyl

′ SO3H NHR Conversion of 3,6-bis(t-butyldimethylsilyl)-N-(3-amino- propyl) normorphine to the corresponding guanidine analog has HN NHR + R′NH2 HN NHR (1) been accomplished in high yield using aminoiminomethanesulfonic acid. Interestingly, all attempts to convert the N atom of mor- Reaction of aminoiminomethanesulfonic acid with a vari- phine directly to the analogous guanidine were unsuccessful.11 ety of amino acids gives yields of guanidino acids rang- Guanylation of the N-(4-aminobutyl)cinnamanilide (3) with ing from 5Ð80%. Reactions of some amino acids do not aminoiminomethanesulfonic acid followed by alkylation with lead to an isolable product. Similar results are obtained with prenyl bromide furnished caracasanamide (4) in high yield (phenylamino)iminomethanesulfonic acid and (phenylamino)- (eq 4).12 Alternatively, (4) could be prepared by reaction of (3) 1 (phenylimino)methanesulfonic acid. with cyanamide (5)12 or from guanylation using the bis-Boc S-methylisothiourea (6) followed by cleavage with TFA.13 Other Nucleophilic Substitution Reactions. Nucleophilic substitution of a variety of substituted aminoiminomethanesulfonic acids with cyanide leads to the corresponding aminoimi- O noethanenitriles in 30Ð87% yield. A number of substituted MeO NH N 2 aminoiminomethanesulfonic acids react with sodium azide in H acetic acid to give the corresponding 5-aminotetrazole. This MeO reaction is subject to pronounced steric hindrance. Hydroxyl- (3) amine and cyanamide also give nucleophilic substitution of the sulfonic acid group.5 Agelasidine-A analogs were prepared in two steps by treatment of a chloroethyl sulfone with ammonia followed by aminoiminomethanesulfonic acid (eq 2). Direct displacement of chloride using guanidine furnished the dienyl analog in comparable yield.6 1. (1), MeOH, rt, 99% 2. prenyl bromide 10% NaOH, 100% BocN SMe NHCN 1. NH3, dioxane, rt, 66% NBoc R O S 2. (1), MeOH, rt, 100% 2 Cl (5) (6)

NH R (2) O2S N NH2 H R = i-Pr, HC=CMe2, Ph O H MeO N NH N H Guanylation of 3R-methyl-L-arginine with aminoimino- HN methanesulfonic acid followed by protection with adamantyloxy- MeO (4) carbonyl chloride produced the bis-Adoc protected arginine deri- (4) vative, a key intermediate in the total synthesis of lavendomycin.7

Avoid Skin Contact with All Reagents 18 p-ANISOLESULFONYL CHLORIDE

Related Reagents. Cyanamide; Guanidine; S-Methyl- Handling, Storage, and Precautions: corrosive and a lachry- isothiourea; O-Methylisourea; 1H-Pyrazole-1-carboxamidine mator. Store at room temperature under anhydrous conditions. Hydrochloride. Use in a fume hood.

Sulfonating Agent. 4-Methoxybenzenesulfonyl chloride has 1. Miller, A. E.; Bischoff, J. J., Synthesis 1986, 777. been employed in the preparation of a wide variety of sulfon- 3,4 2. Kim, K.; Lin, Y.-T.; Mosher, H. S., Tetrahedron Lett. 1988, 29, amides leading to a number of biologically active compounds. 3183. The nonprostanoid thromboxane (TXA2) receptor antagonist 3. Maryanoff, C. A.; Stanzione, R. C.; Plampin, J. N.; Mills, J. E., J. Org. (2) was prepared from the primary amine in the presence of Chem. 1986, 51, 1882. 4-methoxybenzenesulfonyl chloride (1) (1.2 equiv) and excess 4. Muller, G. W.; Walters, D. E.; Du Bois, G. E., J. Med. Chem. 1992, 35, triethylamine (eq 1).3 Arenesulfonyl chlorides have also been used 740. for the synthesis of sulfonyl cyanides5 and arylthiocyanates.6 5. Miller, A. E.; Feeney, D. J.; Ma, Y.;Zarcone, L.; Aziz, M. A.; Magnuson, E., Synth. Commun. 1990, 20, 217. MeO 6. Suryawanshi, S. N.; Rani, A.; Bhakuni, D. S., Indian J. Chem., Sect. B 1991, 30B, 1089. SO2 7. Schmidt, U.; Mundinger, K.; Mangold, R.; Lieberknecht, A., J. Chem. NH2 NH Soc., Chem. Commun. 1990, 1216. S S CO2H CO2H 8. Wityak, J.; Gould, S. J.; Hein, S. J.; Keszler, D. A., J. Org. Chem. 1987, (1) 52, 2179. NEt3 9. Iwanowicz, E. J.; Lin, J.; Roberts, D. G. M.; Michel, I. M.; Seiler, S. M., O (1) Bioorg. Med. Chem. Lett. 1992, 2, 1607. O 10. Dürr, H.; Goodman, M.; Jung, G., Angew. Chem., Int. Ed. Engl. 1992, (2) 31, 785. 11. Jackson, W. R.; Copp, F. C.; Cullen, J. D.; Guyett, F. J.; Rae, I. D.; The addition of sulfonyl chlorides to alkenes in the presence Robinson, A. J.; Pothoulackis, H.; Serelis, A. K.; Wong, M., Clin. of a catalytic amount of dichlorotris(triphenylphosphine)- Exp. Pharmacol. Physiol. 1992, 19,17(Chem. Abstr. 1992, 117,82 ruthenium(II) affords 1:1 adducts.7 Under these reaction 892p). conditions it is believed that sulfonyl radicals, which are conﬁned 12. Crombie, L.; Jarrett, S. R. M., J. Chem. Soc., Perkin Trans. 1 1992, 3179. to the coordination sphere of the metal complex, are involved. 13. Delle Monache, G.; Botta, B.; Delle Monache, F.; Espinal, R.; De When the chiral phosphine (−)-DIOP ((2,3-O-isopropylidene)- Bonnevaux, S. C.; De Luca, C.; Botta, M.; Corelli, F.; Carmignani, M., J. Med. Chem. 1993, 36, 2956. 2,3-dihydroxy-1,4-bis(diphenylphosphino)butane) is used as a ligand, the addition of 4-methoxybenzenesulfonyl chloride to 8 Audrey Miller styrene proceeds to provide the (R) isomer in 40% ee (eq 2). University of Connecticut, Storrs, CT, USA Ru2Cl4 (Ð)-DIOP 3 David C. Palmer + PhCH=CH2 MeO SO2Cl C6H6 R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA H

PhC CH2SO2 OMe (2) Cl p-Anisolesulfonyl Chloride1 Arenesulfonyl chlorides have also been cross-coupled in the presence of Pd0 with both vinyl- and allylstannanes to provide the corresponding sulfones.9 MeO SO2Cl Solvolysis of Arenesulfonyl Chlorides. Kinetics on the [98-68-0] C H ClO S (MW 206.65) solvolysis of various arenesulfonyl chlorides indicate an SN2 7 7 3 mechanism.10,11 InChI = 1/C7H7ClO3S/c1-11-6-2-4-7(5-3-6)12(8,9)10/h2-5H, 1H3 InChIKey = DTJVECUKADWGMO-UHFFFAOYAI 1. Gordon, I. M.; Maskill, H.; Ruasse, M. F., Chem. Soc. Rev. 1989, 18, (versatile sulfonating agent; useful for the preparation of sulfon- 123. amides or as an N-protecting group2) 2. Kitagawa, K.; Kitade, K.; Kiso, Y.; Akita, T.; Funakoshi, S.; Fujii, N.; Yajima, H., J. Chem. Soc., Chem. Commun. 1979, 955. Alternate Name: 4-methoxybenzenesulfonyl chloride. 3. Ohshima, E.; Takami, H.; Sato, H.; Obase, H.; Miki, I.; Ishii, A.; ◦ Physical Data: mp 40Ð43 C. Karasawa, A.; Kubo, K., J. Med. Chem. 1992, 35, 3394. Solubility: sol acetone, acetonitrile, EtOH, MeOH, dioxane, 4. Brown, T. J.; Chapman, R. F.; Mason, J. S.; Palfreyman, M. N.; Vicker, H2O. N.; Walsh, R. J. A., J. Med. Chem. 1993, 36, 1604. Form Supplied in: solid; widely available 98% pure. 5. Vrijland, M. S. A., Org. Synth. 1977, 57, 88.

A list of General Abbreviations appears on the front Endpapers ANTHRACENESULFONAMIDE 19

6. Kagabu, S.; Sawahara, K.; Maehara, M.; Ichihashi, S.; Saito, K., Chem. Synthesis of Protected β-Amino Acids. The synthesis of pro- Pharm. Bull. 1991, 39, 784. tected β-amino acids can be accomplished by treatment of an 7. Kamigata, N.; Ozaki, J.; Kobayashi, M., J. Org. Chem. 1985, 50, imine, generated by treatment of an aldehyde with anthracene- 5045. sulfonamide in the presence of either TiCl4 or Amberlyst 15 (eq 2), t 1 8. Kameyama, M.; Kamigata, N.; Kobayashi, M., Chem. Lett. 1986, 527. with BrZnCH2CO2 Bu in a Reformatsky-like reaction (eq 3). 9. Labadie, S. S., J. Org. Chem. 1989, 54, 2496. 10. Tonnet, M. L.; Hambly, A. N., Aust. J. Chem. 1971, 24, 703. 11. Rogne, O., J. Chem. Soc. (B) 1968, 1294. O a. PhCHO, TiCl4 61% O S NH Raj K. Raheja & Carl R. Johnson 2 or S NPh Wayne State University, Detroit, MI, USA O b. PhCHO, PhH O (2) Amberlyst 15, Δ 70%

Anthracenesulfonamide O t BrZnCH2CO2 Bu S NPh Zn-Cu couple, THF O 66%

S NH2 t O CO2 Bu O S N Ph (3) O H [155495-93-5] C14H11NO2S (MW 257.31) InChI = 1/C14H11NO2S/c15-18(16,17)14-12-7-3-1-5-10(12) 9-11-6-2-4-8-13(11)14/h1-9H,(H2,15,16,17)/f/h15H2 InChIKey = FKFZOFZWJNHJDE-YHSKDTNECL The advantage of using anthracenesulfonamide lies in the more facile reductive cleavage of this group compared to other (readily cleavable reagent for the synthesis of β-amino acids and more traditional N-sulfonyl protecting groups, such as toluenesul- for the iodosulfonamidation of glycals) fonamide or 4-methoxycarbonylbenzenesulfonamide (4-MCBS) (eq 4).1,2 Physical Data: mp 200.5Ð202.5 ◦C. Form Supplied in: yellow solid; synthetically available. CO H CO H Analysis of Reagent Purity: IR (KBr): ν = 3409, 3300, 1312, 1144 2 deprotection 2 −1 1 (4) cm ; H NMR [250 MHz, (CD3)2CO]: δ = 7.0 (br s, 2H), conditions 7.56Ð7.72 (m, 4H) 8.19 (‘d’, J = 9 Hz, 2H), 8.91 (s, 1H), 9.37 RHN Ph H2NPh (‘d’, J = 9 Hz, 2H). Preparative Methods: synthesized from anthracene by sulfona- R Conditions Yield (%) tion with chlorosulfonic acid followed by chlorination with Tosyl TFA then Na/naphth 11 POCl3, then treatment of the crude anthracenesulfonyl chlo- 4-MCBS TFA then Na/naphth 14 1 ride with aq NH3 (eq 1). Anthryl Al/Hg then 1M HCl 63

Optically active β-amino acids have been produced by reaction of the imine generated from anthracenesulfonamide and benzalde- 1. ClSO3H 1. POCl3 SO hyde using lithium and titanium enolates of N-acyloxazolidinones 3 3 2. Bu4NOH 2. NH4OH with limited success (eq 5). In this case, however, better 54% Bu4N 98% results were obtained with the less desirable N-tosyl imine (eq 6).

Iodosulfonamidation of Glycals. Anthracenesulfonamide has been used extensively in the iodosulfonamidation of 4−6 O glycals. This method involves the trans-diaxial addition of N-iodoanthracenesulfonamide to a glycal (eq 7). The so-formed S NH2 (1) O iodosulfonamide can then be converted to a 2-α-anthracenegly- cosamide derivative by the addition of a nucleophile under the appropriate conditions (eq 8).7,8

Avoid Skin Contact with All Reagents 20 ANTHRACENESULFONAMIDE

O O The principle advantage to using anthracenesulfonamide, rather than the more widely employed benzenesulfonamide, is that the ON 1. enolization 2. PhCH=NAnth nitrogen-sulfur linkage can be cleaved under mild conditions, e.g., Me by thiophenol or 1,3-propanedithiol and Hünig’s base. Such mild MePh conditions render this reagent more amenable to solid phase synthesis (eq 9).9−11 In addition, anthracenesulfonamide is more soluble than benzenesulfonamide in THF, a good swelling solvent for O O NHSO2Anth O O NHSO2Anth the polymer, resulting in a more efﬁcient and complete reaction. ON Ph + ON Ph (5) Me Me MePh MePh O I(sym-coll) ClO iPr Si iPr 2 4 Enolization conditions Result O O O TIPSO O AcO O LDA, THF 39% Combined yield (unseparable) O O i TiCl4, EtN Pr2 No reaction OAc S OO NH2 O O

ON 1. enolization Me 2. PhCH=NTs O MePh iPr Si iPr 1. Bu4NN3 2. Ac2O O O O TIPSO I 3. 1,3 propanedithiol O AcO O O O NHTs O O NHTs O O Hünig's base OAc ON Ph ON Ph AnthO2SN + (6) H Me Me MePh MePh

Enolization conditions Result O i iPr Si iPr TiCl4, EtN Pr2 66% anti, 12.5% syn (9) O O O TIPSO O O O O OTIPS AcO O O NH2 O O O OAc AcN I(sym-coll)2ClO4 H OAc O O O O O Related Reagents. Benzenesulfonamide; Toluenesulfon- OAc amide; Mesitylsulfonamide. S OO BnO O BnO NH2 1. Robinson, A. J.; Wyatt, P. B., Tetrahedron 1993, 49, 11329. 2. Arzeno, H. B.; Kemp, D. S., Synthesis 1988, 32. 3. Abrahams, I.; Motevalli, M.; Robinson, A. J.; Wyatt, P. B., Tetrahedron O O OTIPS 1994, 50, 12755. O 4. Danishefsky, S. J.; Bilodeau, M. T., Angew. Chem., Int. Ed. Engl. 1996, O O 35, 1381. OAc O O 5. Arsequell, G.; Valencia, G., Tetrahedron: Asymmetry 1999, 10, 3045. O O O (7) 6. Herzner, H.; Reipen, T.; Schultz, M.; Kunz, H., Chem. Rev. 2000, 100, OAc 4495. I BnO O 7. Danishefsky, S. J.; Roberge, J. Y., Pure & Appl. Chem. 1995, 67, 1647. BnO 8. Danishefsky, S. J.; Hu, S.; Cirillo, P. F.; Eckhardt, M.; Seeberger, P. H., Chem. Eur. J. 1997, 3, 1617. AnthO2SN H 9. Roberge, J. Y.; Beebe, X.; Danishefsky, S. J., Science 1995, 269, 202. 10. Roberge, J. Y.; Beebe, X.; Danishefsky, S. J., J. Am. Chem. Soc. 1998, 120, 3915. O O 11. Savin, K. A.; Woo, J. C. G.; Danishefsky, S. J., J. Org. Chem. 1999, 64, I 4183. O Bu4NN3 BnO O (8) BnO BnO BnO N3 J. David Warren AnthO2SN AnthO2SN Sloan-Kettering Institute for Cancer Research, H H New York, NY, USA

A list of General Abbreviations appears on the front Endpapers 1-BENZENESULFINYL PIPERIDINE 21

in dichloromethane at –60 ◦C in 77% yield (eq 1). On the other hand, reaction of the thioglucoside (5), also bearing the 4,6-O- benzylidene and 2,3-di-O-benzyl protecting groups, under standard conditions with adamantanol (6) provided α-glucoside (7)in 74% yield as a single isomer (eq 2).

O B OBn Ph O O O O O 1-Benzenesulﬁnyl Piperidine BnO + HO SPh O O CMe2 2 3 O S O N 1, Tf2O OBn Ph O O O (1) − O TTBP, CH2Cl2, 60 °C O O 1 77% BnO O

4 O CMe2 [4972-31-0] C11H15NOS (MW 209.31) InChI = 1/C11H15NOS/c13-14(11-7-3-1-4-8-11)12-9-5-2-6-10- Ph O O O 1, Tf2O 12/h1,3-4,7-8H,2,5-6,9-10H2 BnO + HO TTBP, CH Cl , −60 °C InChIKey = LBRJCAJLGAXDKP-UHFFFAOYAQ BnO 2 2 SPh 74% 5 6 (reagent used in combination with trifluoromethanesulfonic anhydride to form a powerful electrophilic salt capable of activating thioglycosides and selenoglycosides for the construction Ph O O O of glycosidic linkages; can also be used for the C-alkylation of BnO (2) β-ketoester enolates) BnO O Alternate Name: BSP. 7 Physical Data: mp 84–85 ◦C. Solubility: soluble in dichloromethane, diethyl ether, toluene, and Low temperature studies have determined that the reaction of most organic solvents. 1 and Tf2O is an equilibrium that favors the starting materials Form Supplied in: off-white solid. over salt 8. However, salt 8 is a very potent thiophile, capable Analysis of Reagent Purity: melting point, NMR spectrum. of converting thioglycosides to glycosyl triflates in a matter of Preparative Methods: a solution of PhSOCl (58.0 g, 0.365 mol) minutes at low temperature. In the presence of thioglycosides, in anhydrous diethyl ether (200 mL) is slowly added to a cooled salt 8 is therefore constantly removed from the equilibrium and solution (5 ◦C) of piperidine (72 mL, 0.73 mmol) in anhydrous the reaction is driven to completion. Finally, the thioglycoside diethyl ether (200 mL). The reaction mixture is stirred at room reacts with the mannosyl triflate in an SN2-like manner to give the 1 temperature for 1 h, filtered, and then concentrated under re- β-mannoside (eq 3). duced pressure. The solid residue is triturated with hexanes to give 1-benzenesulfinyl piperidine (53.4 g, 70%). O TfO OTf Handling, Storage, and Precaution: unknown toxicity. Should be S S N N used within a fumehood. + Tf2O

1 8 Activation of Thioglycosides in Glycosylation Reactions.1 The combination of benzenesulfinyl piperidine (BSP, 1) and tri- OBn Ph O fluoromethanesulfonic anhydride (Tf2O) is a powerful tool for the 2 O O BnO activation of both armed and disarmed thioglycosides in a matter TTBP, CH2Cl2, −60 °C of minutes at low temperature, allowing for the clean conversion OTf to glycosides, upon treatment with alcohols. This reagent com- 9 bination compares favorably with other methods for the activation of thioglycosides as it allows direct access to otherwise diffi- OBn ROH Ph O cult glycosidic linkages such as β-mannosides and α-glucosides O O OR (3) in high yield and stereoselectivity. Thus, reaction of thiomanno- BnO side (2), bearing 4,6-O-benzylidene and 2,3-di-O-benzyl protect- 10 ing groups, with 1/Tf2O, and the non-nucleophilic base, tri-tert- 3 butylpyrimidine (TTBP) reagent combination followed by addi- The BSP/Tf2O reagent combination is not limited to the tion of the glucoside (3) provided β-mannoside (4) within 5 min activation of ether protected thioglycosides. It also activates a

Avoid Skin Contact with All Reagents 22 1-BENZENESULFINYL PIPERIDINE wide range of thioglycosides to give standard glycosidic linkages. disaccharide 23 as a single isomer. Coupling of the acceptor 23 For example, reaction of tetrabenzoyl thiogalactoside (11) under under standard conditions with the thiomannoside donor 24 pre- standard conditions, with the glucoside acceptor 3 furnished ceded smoothly in 92% yield as a 9.6:1 mixture favoring the β- β-galactoside (12) in 78% yield (eq 4).1 In another example, anomer. Deprotection with sodium methoxide followed by 5% reaction of tetrabenzyl thiogalactoside (13) with 3β-cholestanol triﬂuoroacetic acid provided the desired trisaccharide (25) (eq 7). (14), under standard conditions, provided a 1:1 mixture of α:β-galactoside (15) (eq 5). Repeating the reaction mixture in AcO HO AcO O HO O propionitrile as a solvent yielded a 1:4 mixture of the galactoside AcO SPh + BnO 1, Tf2O, TTBP 1 15 favoring the β-anomer (eq 5). NPhth BnO CH2Cl2, −60 °C OMe 85% 16 17 O OBz BzO AcO O O O O AcO O AcO BzO SPh + HO O NPhth AcO (6) OBz O O O CMe2 AcO O AcO BnO 11 3 NPhth BnO O OMe OBz 18 1, Tf2O BzO O O (4) OH − O TTBP, CH2Cl2, 60 °C O N BzO O Ph 2 78% O OBz O O CMe2 O 12 20 O PMBO SPh BSP/Tf2O C8H17 − OBn OPiv CH2Cl2, 60 °C BnO 80% 19 O SPh BnO SPh + TBSO O OBn Ph O HO O 13 14 O O 22 O 1. BSP/Tf O, TTBP C H 2 8 17 HO O CH Cl , −60 °C, 64% NO2 2 2 OPiv 2. TBAF OBn 21 BnO BSP, Tf2O (5) Ph O OPMB Ph O TTBP, CH2Cl2 O BnO O O O −60 °C O PMBO OBn 15 O 24 SPh O X CH Cl , 78%, α:β = 1:1 2 2 OPiv 1. BSP/Tf2O, TTBP α β O − CH3CH2CN, 73%, : = 1:4 HO CH2Cl2, 60 °C, 92% O 2. NaOMe, MeOH/THF The direct synthesis of trisaccharides has also been realized O 3. TFA/CH2Cl2 using the standard reagent combination. Thus, treatment of ◦ 23 the glucosamine donor 16 with BSP/Tf2O/TTBP at −60 Cin X = β -O(CH ) C H -4-NO dichloromethane, followed by addition of 4,6-glucopyranosyl diol 2 4 6 4 2 OH (17) furnished the trisaccharide 18 in 85% yield as a single isomer HO 1 (eq 6). O O X The generality of the BSP/Tf2O glycosylation method has been OH (7) HO OPiv displayed in Crich’s synthesis of the salmonella type E1-core HO O O trisaccharide (25), wherein the three glycosidic bonds were all HO O HO prepared using this methodology.4 Thus, reaction of the thiogalac- OH toside (19) with BSP/Tf2O, in the absence of TTBP, with the alco- 25 hol 20 provided the thiorhamnoside (22) as a single isomer in 80% yield. The acidic conditions of this coupling reaction suppressed The BSP/Tf2O methodology has been used in the ﬁrst example any orthoester formation and affected the removal of the PMB of the direct solid phase synthesis of β-mannosides.5 Treatment protecting group revealing the 3-OH. Treatment of thiorhamno- of thiomannoside (26), bearing a 4,6-O-polystyrylphenylboronate ◦ side (22) with the acceptor 21 under standard coupling condi- group, with BSP/Tf2O/TTBP at −60 C in dichloromethane, tions, followed by deprotection of the silyl group, furnished the followed by the addition of the rhamnosyl acceptor 27 provided

A list of General Abbreviations appears on the front Endpapers